1,721,197 research outputs found
PI3K/Akt signalling pathway specific inhibitors: A novel strategy to sensitize cancer cells to anti-cancer drugs
No full textThe resistance of many types of cancer to chemotherapies represents the major hurdle in successful cancer treatment. Cancer cells can escape the toxic effect of most commonly used drugs despite their different chemical structure and intracellular targets. The mechanisms underlying the failure of chemotherapeutic drugs have been well studied. Here I review the role of a signalling pathway activated by the lipid kinase phosphoinositide 3-kinase (PI3K) and the serine/threonine kinase, protein kinase B (PKB) or Akt, in chemotherapeutic resistance. Activation of this pathway plays a key role in different cellular functions such as growth, migration, survival and differentiation. Data accumulated in the last decade have established that this pathway plays a key role in cancer development and progression. More recently it has been shown that this pathway plays also a key role in resistance to chemotherapy. Therefore drugs designed to specifically target this pathway are under development to be used as single agent and in combination to chemotherapy to overcome therapeutic resistance. © 2010 Bentham Science Publishers Ltd
Anti-cancer activity of the bioactive compound inositol pentakisphosphate
No full textBioactive compounds are extra nutritional constituents found in small quantities in foods. We have recently shown that a bioactive compound, inositol pentakisphosphate (IP5), a naturally occurring substance that is present in most legumes, wheat bran and nuts, inhibits cell growth of ovarian, lung and breast cancer cells. We demonstrated that IP5 specifically blocks the activation of the critical phosphoinositide 3-kinase (PI3K) effector Akt, a serine/threonine kinase which plays a key role in different intracellular processes such as cell survival and proliferation. Due to its role in cancer development and progression, the PI3K/Akt pathway is an attractive target for therapeutic intervention. Interestingly, IP5 possesses anti tumour activity in mice to the same extent than cytotoxic drug cisplatin. Furthermore, IP5 enhances the effect of cytotoxic drugs in ovarian and lung cancer cells. These results support a role for IP5 as an anti-tumour agent that may sensitise cancer cells to the action of commonly used anti-cancer drugs. In addition we have recently observed that specific modifications of the IP5 structure may result in compounds with the same solubility and lack of toxicity in vivo but broader range of action and a higher activity compared to parental molecule indicating that IP5 may represents a promising molecule for further development of novel anticancer drugs. Therefore, our study reveals a new pharmacologically active nutrient (nutraceutical) as a potential chemopreventive agent and a lead compound for possible development of potent small molecule PI3K/Akt inhibitors. © 2009 Springer Science+Business Media B.V
Phosphoinositide 3-kinase-dependent regulation of phospholipase Cγ
No full textActivation of the enzyme PLC (phospholipase C) leads to the formation of second messengers Ins(1,4,5)P3 and diacylglycerol. RTKs (receptor tyrosine kinases) activate this reaction through PLCγ isoenzymes. It has been shown that PI3K (phosphoinositide 3-kinase) may regulate PLCγ activity through the interaction of PI3K product PtdIns(3,4,5)P3 and the PLCγ PH domain (pleckstrin homology domain). Here, we analyse the potential functional roles of the PI3K/PLC pathway. ©2007 Biochemical Society
Patterns within protein/polyphosphoinositide interactions provide specific targets for therapeutic intervention
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Emerging roles of phosphatidylinositol 3-monophosphate as a dynamic lipid second messenger
No full textElevated levels and mitogenic activity of lysophosphatidylinositol in k-ras-transformed epithelial cells
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